Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids

Abstract
Importance: Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids.

Objective: To examine the risks associated with cannabis use among adults prescribed opioid analgesic medications.

Design, Setting, and Participants: This cohort study was conducted among individuals aged 18 years and older who had urine drug screening in 2014 to 2019 and received any prescription opioid in the prior 90 days or long-term opioid therapy (LTOT), defined as more than 84 days of the prior 90 days, through the Veterans Affairs health system. Data were analyzed from November 2020 through March 2022.

Exposures: Biologically verified cannabis use from a urine drug screen.

Main Outcomes and Measures: The main outcomes were 90-day and 180-day all-cause mortality. A composite outcome of all-cause emergency department (ED) visits, all-cause hospitalization, or all-cause mortality was a secondary outcome. Weights based on the propensity score were used to reduce confounding, and hazard ratios [HRs] were estimated using Cox proportional hazards regression models. Analyses were conducted among the overall sample of patients who received any prescription opioid in the prior 90 days and were repeated among those who received LTOT. Analyses were repeated among adults aged 65 years and older.

Results: Among 297 620 adults treated with opioids, 30 514 individuals used cannabis (mean [SE] age, 57.8 [10.5] years; 28 784 [94.3%] men) and 267 106 adults did not (mean [SE] age, 62.3 [12.3] years; P < .001; 247 684 [92.7%] men; P < .001). Among all patients, cannabis use was not associated with increased all-cause mortality at 90 days (HR, 1.07; 95% CI, 0.92-1.22) or 180 days (HR, 1.00; 95% CI, 0.90-1.10) but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.01-1.07) and 180 days (HR, 1.04; 95% CI, 1.01-1.06). Among 181 096 adults receiving LTOT, cannabis use was not associated with increased risk of all-cause mortality at 90 or 180 days but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.02-1.09) and 180 days (HR, 1.05; 95% CI, 1.02-1.09). Among 77 791 adults aged 65 years and older receiving LTOT, cannabis use was associated with increased 90-day mortality (HR, 1.55; 95% CI, 1.17-2.04).

Conclusions and Relevance: This study found that cannabis use among adults receiving opioid analgesic medications was not associated with any change in mortality risk but was associated with a small increased risk of adverse outcomes and that short-term risks were higher among older adults receiving LTOT.